Exon array analysis of head and neck cancers identifies a hypoxia related splice variant of LAMA3 associated with a poor prognosis.

PLoS Computational Biology
Carla S Moller-LevetCrispin J Miller

Abstract

The identification of alternatively spliced transcript variants specific to particular biological processes in tumours should increase our understanding of cancer. Hypoxia is an important factor in cancer biology, and associated splice variants may present new markers to help with planning treatment. A method was developed to analyse alternative splicing in exon array data, using probeset multiplicity to identify genes with changes in expression across their loci, and a combination of the splicing index and a new metric based on the variation of reliability weighted fold changes to detect changes in the splicing patterns. The approach was validated on a cancer/normal sample dataset in which alternative splicing events had been confirmed using RT-PCR. We then analysed ten head and neck squamous cell carcinomas using exon arrays and identified differentially expressed splice variants in five samples with high versus five with low levels of hypoxia-associated genes. The analysis identified a splice variant of LAMA3 (Laminin alpha 3), LAMA3-A, known to be involved in tumour cell invasion and progression. The full-length transcript of the gene (LAMA3-B) did not appear to be hypoxia-associated. The results were confirmed using qualit...Continue Reading

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Nov 29, 2013·International Journal of Cell Biology·Serena BonomiClaudia Ghigna
Oct 12, 2012·Journal of Cell Communication and Signaling·Michael JewerLynne-Marie Postovit
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Jul 20, 2019·Medical Oncology·Ali Mohamed AlshabiChanabasayya Vastrad
Jun 17, 2020·Journal of Experimental & Clinical Cancer Research : CR·Antonietta Rosella FarinaAndrew Reay Mackay

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Datasets Mentioned

BETA
GSE18300
ENST00000381545

Methods Mentioned

BETA
chips
PCA
PCR

Software Mentioned

Map
MADS
DAVID
FIRMA
RMA
ENSEMBL
SDS2
PLIER
Exonmap
GeNorm

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